A specific reagent to study trypanosomatids respiration through polyprenyl diphosphate synthases inhibition: 1-[(n-oct-1-ylamino) ethyl] 1,1-bisphosphonic acid.

Octavio Fusco; Cristina Soraires; Alicia Hoffer; Alicia G. Fuchs; Alina Perrone; Patricia Garavaglia; Bruno Travi; Juan Carlos Engel; Laurence Lecordier; Laura Fichera; Cristina Maidana; Victoria Fragueiro Frías; Gabriela A. García; Jacqueline Bua; Sergio H. Szajnman; Juan Bautista Rodríguez; Romina Rebozzio; Mónica Esteva; Carlos Pravia; Benoît Vanhollebeke; Esteban Bontempi

doi:10.59471/202324

Authors

Octavio Fusco Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0001-6100-8055
Cristina Soraires Pharmacology Department and IQUIMEFA (CONICET-FFYB), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires 1113, Argentina Author https://orcid.org/0000-0003-1779-4903
Alicia Hoffer Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-3017-2511
Alicia G. Fuchs Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0003-3621-6551
Alina Perrone Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0001-6398-7031
Patricia Garavaglia Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-7947-6938
Bruno Travi Depts. of Internal Medicine & Microbiology and Immunology, University of Texas Medical Branch (UTMB), Galveston, Texas 77555-0435, USA Author https://orcid.org/0000-0003-4160-302X
Juan Carlos Engel Sandler Center for Basic Research in Parasitic Diseases and Department of Pathology, University of California, San Francisco, California 94158-2330, USA Author
Laurence Lecordier Laboratory of Molecular Parasitology, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, Gosselies B-6041, Belgium Author https://orcid.org/0000-0003-0604-5819
Laura Fichera Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-2089-0659
Cristina Maidana Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-0173-8862
Victoria Fragueiro Frías Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-3147-3762
Gabriela A. García Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-6272-6443
Jacqueline Bua Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0001-8373-4031
Sergio H. Szajnman Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires 1428, Argentina Author https://orcid.org/0000-0001-6989-4768
Juan Bautista Rodríguez Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires 1428, Argentina Author https://orcid.org/0000-0002-5180-096X
Romina Rebozzio Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-8539-0452
Mónica Esteva Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-7817-7848
Carlos Pravia Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0002-7929-291X
Benoît Vanhollebeke Laboratory of Molecular Parasitology, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, Gosselies B-6041, Belgium Author https://orcid.org/0000-0002-0353-365X
Esteban Bontempi Instituto Nacional de Parasitología “Dr. M. Fatala Chaben”, A.N.L.I.S/Malbrán, Secretaría de Salud, Buenos Aires 1063, Argentina Author https://orcid.org/0000-0001-8182-2089

DOI:

https://doi.org/10.59471/202324

Keywords:

Trypanosoma cruzi, Trypanosoma brucei, Leishmania, lanesyl diphosphate synthase, ubiquinone, inhibitor, bisphosphonate, EC50, LC50

Abstract

Background: Ubiquinone or Coenzyme Q (CoQ) is a molecule performing an essential function as an electron carrier in the respiratory chain. Besides, it functions as a proton and electron acceptor and as an antioxidant. It is composed of a benzoquinone ring and an isoprenoid chain, the last one being synthesized by a polyprenil diphosphate synthase. The inhibition of the Trypanosoma cruzi enzyme by 1-[(n-oct-1-ylamino) ethyl] 1,1-bisphosphonic acid (OBA) is lethal, as well as the interference of the homologous enzyme in T. brucei brucei. We now studied the OBA sensitivities of the different forms of human pathogenic trypanosomatids.

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